The title of a recent paper in the Journal of the American Chemical Society, or JACS for short, is: Ecological Niche-Inspired Genome Mining Leads to the Discovery of Crop-Protecting Non-ribosomal Lipopeptides Featuring a Transient Amino Acid Building Block. JACS publishes heavy stuff. Readers may think these authors and JACS are on a one-lane road to obscurity, but there is substance here. A shorter title might have been Antibiotics from Pseudomonas Kill Nasty Amoebae and Fungi. The authors named the class of antibiotics after Keanu Reeves, the Canadian actor who plays retired assassin, John Wick, who emerges to kill bad guys. Amoebae and fungi cause many diseases, and they are all bad guys because forestry, agriculture, and medicine have few defenses against them. Fungi kill our crops and trees in periodic waves. I want our ash, chestnut, hemlock, and elm trees back, or at least to give them a fighting chance.
The Jena people, led by Dr. Pierre Stallforth, use a strategy that lets evolution do much of the work. They looked for antibiotics in biological situations where two or more species have fallen into an equilibrium, a condition called either mutualism or competition. They reasoned that one species may make an antibiotic or natural product to compete.
Amoeba-like cells have a lot of internal architecture: vacuoles, nuclei, sites to make special proteins, structures to carry out tasks of digestion and energy production, and ways to recognize harmful bacteria and pull them inside. These cells crawl over the surface of our lungs, peritoneum, and kidneys. They clean up bacteria and debris after inflammation. In the lungs they are called alveolar macrophages, but they patrol almost everywhere. All higher organisms have amoebae or similar cells; they are an essential cellular life form that evolution has kept. Some amoebae can also cause disease; think of amoebic dysentery or the brain destroying amoebae that people get in warm freshwater ponds.
Some amoebae live in a special vacuole, surrounded by a membrane, where they have acquired the ability to interrupt a process that normally kills them. Mycobacterium tuberculosis and Legionella pneumoniae live in such cellular compartments, where they grow and divide. The Stallforth lab uses a species called Dictyostelium discoideum that lives in soil and eats the many bacteria they find there. Legionella and TB bacteria flourish in Dictyostelium the vacuoles of these amoebae.
Your columnist and his lab studied Dictyostelium for decades and wrote a book on these shapeshifting, complicated, and quite beautiful creatures. Type ‘John Bonner and Princeton’ into a browser and you will find a lovely film, made in 1947. Albert Einstein asked to see it. There is more to this story, but let’s return to Dr. Stallworth.
Instead of isolating bacteria or amoebae from this niche and asking if individual bacteria or amoebae produced antibiotics, they extracted DNA and examined the sequences of A, C, G, and T of millions of individual genes. It sounds hard, and it was once, but now the process is efficient and automated. Two classes of genes make the enzymes to produce antibiotics, each easily recognized by their DNA sequences stored in enormous databases. The group found one of them in the bacteria called Pseudomonas.
The story of our niche takes us back to the experimental forest of the University of Virginia in the Great Smoky Mountains, where, in 2014, evolutionary biologists Joan Strassmann and David Quellar of Washington University were looking for new strains of Dictyostelium.
Joan found a fruiting body of Dictyostelium, which looks like a lollipop about 1mm high, but it was on a steaming pile of deer scat. Where the business end of the lollipop would be, there was a ball of tough spores, about 50,000 held in a drop by surface tension. Fruiting bodies form in the lab, but that was the first time one had been seen in the wild. In the liquid around the spores there were bacteria, a strain of Pseudomonas, now called QS1027 (Queller-Strassmann), that we now know secretes antibiotics.
Let me leave you with Professor Joan Strassmann, author of a recent book called Slow Birding, a member of The National Academic of Sciences, a teacher and mentor, on hands and knees with her nose six inches from a heap of deer poop, yelling in delight. Joy is where you find it.
Richard Kessin, Ph.D, is Emeritus Professor of Pathology and Cell Biology in the Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University Irving Medical center. His columns are at RichardKessin.com.
